Project Summary Age-related macular degeneration remains the most common cause of permanent vision loss in the US and many industrialized countries. Extensive attention is paid to developing treatments, resulting in 680 registered treatment trials in the US. The large numbers of patients and trials accentuates the need for improved biomarkers for the management of patients. Further, if outcome measures, including visual acuity, could be made more accurate and have decreased test-retest variability, then clinical trials could use smaller sample sizes. This leads to a savings in cost and time to bring therapies to market. We will minimize the issues from the optics of the aging eye by building a Maxwellian view device with a low cost but high resolution display suitable for visual acuity testing. Simultaneous retinal imaging and onboard focus will decrease the artifact from target defocus from retinal elevation due to exudative age-related macular degeneration. The part of the retina that is used for visual acuity will be localized. Related devices for microperimetry are more expensive and lack the resolution needed for visual acuity. We will use psychophysical techniques that are rapid, accurate, and provide better measures of variability: 2 alternative forced choice with Method of Constant Stimuli and ZEST. In Aim 1, we will build a version of the digital light ophthalmoscope (DLO) that has a high resolution visual display and NIR illumination for retinal imaging. The imaging light is comfortable and dim enough not to interfere with visual tasks. The DLO projects a series of stripes onto the retina in a raster pattern, providing line scanning for imaging, therefore increasing contrast even in the aging eye and exudation. The detection is via a 2D CMOS detector with a rolling shutter, with the serial read-out of the lines either synchronized with the illumination or offset in time. This provides a flexible electronic aperture under computer control. Both confocal and multiply scattered light images are available during visual function testing, revealing drusen and other subretinal deposits, or locations of sub-retinal treatment. We will optimize image quality and autofocus ability in 10 subjects with a range of refractive error, ocular pigmentation, and age. In Aim 2, we will optimize our novel method of visual acuity measurement. To model performance in aging eyes or those with macular degeneration, we will measure at 20/20 and also degrade vision in 40 subjects with Bangerter foils to 20/40, 20/60 and 20/80 and compare to ETDRS charts, then test with spatial pattern noise that masks the letters. In Aim 3, we will develop new software that is robust in aging eyes to support a variety of visual function tests, capable of focusing and registering visual targets to a specific location on the retina. We will test 20 normal subjects, and 10 patients with age-related macular degeneration. This project can move high quality visual testing into clinical trials, research facilities, and eventually the lane.